Kainic acid (KA), a structural analogue of glutamic acid, has been proposed as specifically destroying cell bodies possessing glutamate receptors while sparing fibers of passage. Its presumed selectivity underlies the use of KA to produce models of neurological disorders such as Huntington's disease and to study effects of destruction of specific cell populations. The selectivity of this agent's neurotoxicity, which requires further investigation, could be evaluated independently in the cerebellum where the putative glutamatergic neurons develop postnatally and are identifiable morphologically. The objectives of this proposal, therefore, are (1) to assess the specificity of KA neurotoxicity in the cerebellum, and (2) to evaluate the proposed mechanism of KA action by establishing the extent of correlation between development of cerebellar glutamatergic innervation and the severity of KA neurotoxicity. Injection of KA into the mouse cerebellum at 5, 10, 15 and 25 days of age will be followed by light and electron microscopic examination and by assessment of changes in neurotransmitter systems. Distinctions between primary and secondary actions of KA will be evaluated by comparing the pathology at different intervals after injection. Alterations in both morphology and neurotransmitter biochemistry will be used to define KA-induced damage to afferent axonal terminals and intrinsic cell populations. The results will assess the usefulness of KA as a specific lesioning agent by determining whether KA damages afferent cerebellar fibers or gluatmatergic neurons. Correlation of the severity of Purkinje cell pathological reactions with time of KA injection will clarify the extent to which KA may act via effects on glutamate receptors. Finally, the extent to which KA can be useful in future research directed toward investigating aberrant synaptic development and dysfunction or clarifying the pathogenesis of certain neurological disorders will be evaluated.